This application for a Physician Scientist Award is intended to enable the candidate to become an independent researcher in neurobiology, with expertise in molecular genetic approaches and a focus on problems of particular relevance to aging, such as Alzheimer's disease. Phase I will include a program of independent reading designed by the sponsor, Dr. David Patterson, auditing courses at the University of Colorado Health Sciences Center, and attending seminars there and at the Eleanor Roosevelt Institute, and will involve the candidate in laboratory projects currently underway in Dr. Patterson's laboratory in order to learn the techniques of molecular genetics. These projects include development of a somatic cell hybrid model for examination of the expression of the amyloid precursor protein gene and the function of the various forms of the protein it encodes, isolation and identification of the proteins bound by the serine protease inhibitor domain of the amyloid precursor protein, and more exact definition of the genetic material required for phenotypic Down's syndrome. In Phase II the candidate will continue work on Alzheimer disease and will begin an examination of the molecular genetics of amyotrophic lateral sclerosis. The candidate's ultimate goal is an academic career in neurology, with research on neurodegenerative diseases.